title: Neural hyperactivation in carriers of the Alzheimer's risk variant on the clusterin gene.
abstract: Recent GWAS identified a risk variant for Alzheimer's disease (AD) at a locus (rs11136000) of the clusterin gene (CLU). Here we use functional magnetic resonance imaging (fMRI) during working memory to probe the effect of the risk variant on brain activation in healthy individuals. Participants with the CLU risk genotype had higher activity than participants with the protective allele in frontal and posterior cingulate cortex and the hippocampus, particularly during high memory demand. These results inform pathophysiological models of the preclinical progression of AD.
authors.affiliation: School of Medical Sciences, Bangor University, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lancaster
authors.forename: Alison
authors.initials: A
authors.lastname: Baird
authors.forename: Claudia
authors.initials: C
authors.lastname: Wolf
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Jackson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Johnston
authors.forename: Rossen
authors.initials: R
authors.lastname: Donev
authors.forename: Johannes
authors.initials: J
authors.lastname: Thome
authors.forename: David E J
authors.initials: DE
authors.lastname: Linden
mesh_terms: D000293:Adolescent; D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D051152:Clusterin / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
chemical_list: C495242:CLU protein, human; D051152:Clusterin